Trastuzumab beyond progression: a cost-utility analysis

Background: The continuation of trastuzumab beyond progression in combination with capecitabine as secondary chemotherapy for HER2-positive metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase in toxicity. Patients and methods: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the Breast International Group 03-05 clinical trial. Direct costs were assessed from the perspective of the Swiss health care system. Results: The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33 980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98 329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60 000/QALY was reached in 12% of cases. Conclusion: The addition of trastuzumab to capecitabine in MBC patients is more expensive than what is typically regarded as cost-effective but falls within the value ranges found for established regimens in the treatment of MB

NG7538 IRS1 N: modeling a circumstellar maser disk

We present an edge-on Keplerian disk model to explain the main component of the 12.2 and 6.7 GHz methanol maser emission detected toward NGC7538-IRS1 N. The brightness distribution and spectrum of the line of bright masers are successfully modeled with high amplification of background radio continuum emission along velocity coherent paths through a maser disk. The bend seen in the position-velocity diagram is a characteristic signature of differentially rotating disks. For a central mass of 30 solar masses, suggested by other observations, our model fixes the masing disk to have inner and outer radii of about 270 AU and 750 AU.Comment: To appear in The Proceedings of the 2004 European Workshop: "Dense Molecular Gas around Protostars and in Galatic Nuclei", Eds. Y. Hagiwara, W.A. Baan, H.J. van Langevelde, 2004, a special issue of ApSS, Kluwe

Selective Intra-arterial Chemotherapy with Floxuridine as Second- or Third-Line Approach in Patients with Unresectable Colorectal Liver Metastases

Background: An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). Methods: Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. Results: Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6months (range, 2.5-55.7months), 3.9months (range, 0.7-55.7months), and 5.5months (range, 1.6-55.7months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P=0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P=0.09). No differences were observed in OS (P=0.69) or PFS (P=0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P<0.0001). Toxicities were manageable with dose modifications and supportive measures. Conclusions: FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsize

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31-72) and of 18% (95%CI 10-30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. NCT00004935 ; first posted 27.01.2003, retrospectively registered

Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial

Background: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. Patients and methods: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m2 day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m2 d1) and capecitabine (650-800 mg/m2 b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. Results: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m2 d1, d8; oxaliplatin 130 mg/m2 d1 and capecitabine 650 mg/m2 b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. Conclusion: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigation